Summary
H1-antihistamines have been used in treatment of allergic disorders for more than 30 years. However, many of them have been employed in a less than systematic fashion. Most of the antihistamines show an apparent dual mechanism of action on isolated organs, consisting of a competitive and a non-competitive component. To induce non-competitive antagonism, higher concentrations are usually required, but for dimethindene the dose ratios for competitive and non-competitive activities differed only by less than one log unit. For therapeutic guidelines it should be considered that some antihistamines loose their effectiveness under long-term treatment and that patients may complain about the sedative side-effects. Thus, for maximum benefit it sometimes appears necessary to change the preparation before a choice for the individual dose is finally made. Under this condition they will cause relief from many allergic symptoms. Nevertheless, the classical antihistamines are without effect in bronchial asthma. The search for new drugs has been successful in this direction, as it has shown the antihistaminic/antiallergic drug Ketotifen to be able to prevent and control bronchial asthma. Many commercial preparations used in the treatment of common cold, vomitus or rhinitis contain an additive in combination with the antihistamines. Some of the additives appear to be of some value since they are used to reduce the side-effects of antihistamines. Secondary pharmacological properties of the antihistamines however provide also additional uses. This holds especially for effects on the CNS. Together with the search for the role played by histamine in the central cell-to-cell communication, new drugs might be found which will inhibit more selectively the action of histamine in the CNS.
Zusammenfassung
Die H1-Antihistaminika werden seit über 30 Jahren zur Behandlung allergischer Erkrankungen eingesetzt. Viele von ihnen sind bisher jedoch noch nicht systematisch untersucht worden. Antihistaminika üben gegenüber der Histaminwirkung an isolierten Organen einen dualistischen Effekt aus, der aus einer kompetitiven und einer nicht-kompetitiven Komponente besteht. Zur Auslösung des nicht-kompetitiven Antagonismus sind gewöhnlich wesentlich höhere Dosen erforderlich, für das Dimethinden unterscheiden sich jedoch die Dosen zur Auslösung des kompetitiven und des nicht-kompetitiven Antagonismus nur um etwa 1 log Einheit.
Bei der Therapie mit Antihistaminika muß berücksichtigt werden, daß einige bei Langzeitanwendung ihre Wirksamkeit verlieren und daß die sedierenden Effekte oft zu einer wesentlichen Beeinträchtigung führen. Es erscheint daher sinnvoll, zur Individualisierung der Therapie gegebenenfalls das Präparat zu wechseln, bevor das endgültige Therapieschema erstellt wird. Unter diesen Voraussetzungen sind die Antihistaminika erfolgreich bei vielen allergischen Erkrankungen einzusetzen. Beim Asthma bronchiale sind die klassischen Substanzen jedoch unwirksam. Die Suche nach neuen Wirkstoffen hat insofern zum Erfolg geführt, als mit dem Ketotifen ein neues wirksames Antihistaminikum/Antiallergikum zur Behandlung des Asthma bronchiale zur Verfügung steht.
Viele Präparate, die bei der Behandlung “grippaler Infekte”, bei Vomitus und Rhinitiden eingesetzt werden, enthalten zusätzlich zum Antihistaminikum andere Pharmaka, die teilweise die unerwünschten Nebenwirkungen reduzieren sollen.
Die Nebenwirkungen einiger Antihistaminika haben jedoch das Wirkungsspektrum andererseits erweitert. Dies gilt insbesondere für die zentralnervösen Effekte. Zusammen mit der weiteren Aufklärung der Funktion von Histamin als zentralnervöser Überträgersubstanz wird man bestrebt sein, Antihistaminika zu synthetisieren, die selektiver die zentralen Wirkungen des Histamins zu blockieren vermögen.
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Dedicated to Prof. Dr. G.-A. von Harnack in the occasion of the 65th birthday
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Reinhardt, D., Borchard, U. H1-receptor antagonists: Comparative pharmacology and clinical use. Klin Wochenschr 60, 983–990 (1982). https://doi.org/10.1007/BF01716959
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DOI: https://doi.org/10.1007/BF01716959